Formation of neurofibrillary tangles in P301L tau transgenic mice induced by A beta 42 fibrils

beta -Amyloid plaques and neurofibrillary tangles (NFTs) are the defining n europathological hallmarks of Alzheimer's disease, but their pathophysiolog ical relation is unclear. Injection of beta -amyloid A beta (42) fibrils in to the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neuro ns project to the injection sites. Gallyas silver impregnation identified N FTs that contained tau phosphorylated at serine 212/threonine 214 and serin e 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after A beta (42) injections. Our data support the hypothesis that A beta (42) fibrils can accelerate NFT formation in vivo.